The frequency of multi-drug resistant infections is increasing at an alarming rate. Equally concerning is the limited therapeutic options available for effective treatment, resulting in increased morbidity and mortality associated with these highly resistant infections. Frequently, multi-drug resistant infections manifest as soft tissue or wound infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and other multi-drug resistant bacteria. The proposed project focuses on the development of a non-toxic, topical rinse product. This wound decontaminant is capable of helping to clear bacteria from wound, killing a broad spectrum of resistant and non-resistant bacteria, and providing a residual prophylactic effect that prevents bacterial colonization. By aggregating bacteria, the infectious pathogens are more easily rinsed from the wound. Any bacteria not removed are killed by the polymer derivative and residual material prevents bacterial colonization. This proposed work optimizes the concentration required and specific molecular weight formulation of the molecule to facilitate wound cleaning and protection from subsequent infection. These studies will lead to in vivo studies in Phase II in support of required regulatory applications. The goal is to provide a novel, highly effective and highly biocompatible therapy for the treatment and prevention of wound infections, particularly addressing bacteria that are multi-drug resistant. PUBLIC HEALTH RELEVANCE: A natural antimicrobial polymer derivative has been developed that demonstrates broad-spectrum antibacterial activity against multi-drug resistant and non-resistant bacteria. The polymer is a biocompatible, non-toxic polysaccharide, is not absorbed or metabolized by the body, and is ideal for topical applications. Further, because the mechanism of action of the molecule with bacteria is physical membrane damage, the polymer is less likely to evoke antibiotic resistance. Our aims focus on the characterization and development of a non-toxic, efficacious wound decontamination rinse for prevention and treatment of multi-drug resistant wound infections. The optimized formulation is expected to facilitate the removal of pathogenic bacteria via clumping, reducing the viability of remaining bacteria and providing a limited residual barrier to bacterial colonization. This proposed research is intended to understand and optimize the molecular variables associated with clumping, bactericide and residual effect and ultimately provide a novel therapeutic product to prevent and treat multi-drug resistant wound infections.